inotodiol and Disease-Models--Animal

Inotodiol has been proven to have antitumor, antiviral, anti-inflammatory, and antiallergic properties. This study investigated the immunomodulatory capability of inotodiol in allergic rhinitis (AR) mice.. Forty BALB/c mice were divided into four groups, 10 mice each: control (CON), AR with phosphate-buffered saline (PBS) treatment (AR), inotodiol treatment (AR+Ino), and dexamethasone treatment (AR+Dex). Episodes of sneezing and nose rubbing were counted. Cytokines in nasal lavage fluid (NLF) and immunoglobulin in blood serum were measured. Nasal mucosae from each group were used for protein, reverse transcriptase-polymerase chain reaction (RT-PCR), and histological analyses. Splenocytes were cultured for evaluation of cytokine production in each group.. Symptoms of rubbing and sneezing improved in the group of AR+Ino and AR+Dex than in the AR. NLF in the AR+Ino and AR+Dex also showed a significant decrease in interleukin (IL)-5, IL-10, and IL-13 compared to the AR. In addition, the number of eosinophils, goblet cells, and mast cells were notably lower in the nasal mucosae of the AR+Ino and AR+Dex. IL-4 and IL-17A in the AR+Ino and AR+Dex groups were decreased compared to the AR. Chemokines related to mast cell degradation were also decreased in the AR+Ino and AR+Dex groups. Total immunoglobulin (Ig)E, specific IgE and ovalbumin (OVA)-specific IgG1, and histamine levels were also significantly lower in the AR+Ino and AR+Dex groups. IL-10 and IL-13 were notably increased in the splenocytes of the AR after OVA stimulation, whereas the other groups showed no change.. These results indicate inotodiol can help suppress allergic responses by immunomodulation activities.

Topics: Animals; Cytokines; Disease Models, Animal; Immunoglobulin E; Inflammation; Interleukin-10; Interleukin-13; Mice; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Rhinitis, Allergic; Sneezing

While inhaled corticosteroids (ICSs) are the mainstay of asthma treatment, due to compliance, drug safety, and resistance issues, new medications to replace ICSs are in high demand. Inotodiol, a fungal triterpenoid, showed a unique immunosuppressive property with a preference for mast cells. It exerted a mast cell-stabilizing activity equally potent to dexamethasone in mouse anaphylaxis models when orally administered in a lipid-based formulation, upgrading bioavailability. However, it was four to over ten times less effective in suppressing other immune cell subsets, depending on the subsets, than dexamethasone showing invariably potent inhibition. Accordingly, inotodiol affected the membrane-proximal signaling for activating mast cell functions more profoundly than other subsets. Inotodiol also effectively prevented asthma exacerbation. Importantly, considering the no-observed-adverse-effect level of inotodiol was over 15 times higher than dexamethasone, its therapeutic index would be at least eight times better,implying that inotodiol is a viable option for replacing CSs in treating asthma.

Topics: Animals; Anti-Asthmatic Agents; Asthma; Dexamethasone; Disease Models, Animal; Mast Cells; Mice

Chaga mushroom (

Topics: Animals; Anti-Inflammatory Agents; Disease Models, Animal; Inonotus; Lanosterol; Mice; Triterpenes

Inotodiol is a lanostane triterpenoid found only in Chaga mushroom. In the previous study investigating anti-allergic effects of fractionated Chaga mushroom extracts, we have found evidence that purified inotodiol holds an activity to suppress the mast cell function in vivo. To address the therapeutic relevance of the finding, in this study, we investigated whether inotodiol could also alleviate allergy symptoms observed in a chicken ovalbumin (cOVA)-induced mouse model of food allergy. Like the crude 70% ethanol extract of Chaga mushroom (320 mg/kg), oral administration of inotodiol (20 mg/kg), regardless of whether that was for preventive or treatment purpose, resulted in a significant improvement in allergic symptoms and inflammatory lesions in the small intestine appearing after repeated oral challenge with cOVA. Despite the results that inotodiol (20 mg/kg) and the Chaga mushroom extract (320 mg/kg) took effect to a similar extent, immunological mechanisms underlying those effects were found to be distinct from each other. That is, the results obtained from several in vivo assays, including mast cell-mediated passive systemic anaphylaxis, activation/proliferation of adoptively transferred antigen-specific T cells and immunoglobulin (IgG1, IgE, IgA) production by antigen-specific B cells, illustrated that inotodiol selectively inhibited the mast cell function without having any noticeable effect on other immune responses while the crude Chaga mushroom extract indiscriminately suppressed diverse immune responses. The strong anti-allergic activity of inotodiol, along with its remarkable selectivity to mast cell, makes it an excellent therapeutic candidate for food allergy with both high efficacy and outstanding safety.

Topics: Allergens; Animals; Anti-Allergic Agents; Cell Degranulation; Disease Models, Animal; Food Hypersensitivity; Humans; Inonotus; Lanosterol; Mast Cells; Mice; Mice, Inbred BALB C; Ovalbumin; Triterpenes

While an anti-allergic effect of Chaga mushroom (Inonotus obliquus) has been indicated, its therapeutic effect on allergy and immunoregulatory mechanisms and chemical constituents directly responsible for that are hardly known. We examined the effect of 70% ethanol extract of Chaga mushroom (EE) and its dichloromethane (DF) and aqueous (AF) fractions using a mouse model of chicken ovalbumin (cOVA)-induced food allergy, and found that only EE and DF ameliorated allergy symptoms to a significant extent. The in vivo mast cell-stabilizing activity was also found only in EE and DF whereas the activities to suppress Th2 and Th17 immune responses and cOVA-specific IgE production in the small intestine were observed in all three treatment regimens, implying that inhibition of the mast cell function by lipophilic compounds was vital for the therapeutic effect. Results also indicated that inotodiol, a triterpenoid predominantly present in DF, played an active role as a mast cell stabilizer.

Topics: Animals; Anti-Allergic Agents; Basidiomycota; Disease Models, Animal; Ethanol; Female; Food Hypersensitivity; Humans; Immunoglobulin E; Lanosterol; Mast Cells; Methylene Chloride; Mice; Mice, Inbred BALB C; Ovalbumin; Th17 Cells; Th2 Cells

Breast cancer is amongst the most common cancers causing death of women worldwide. Breast cancer occurrence is more prominent in people with diabetes. A recent trend is management of diabetes and cancer has evolved to be natural remedy including single molecule therapy or combination. In this study, we investigated the effect of inotodiol on breast cancer growth in diabetic conditions. Inotodiol is a lanostane triterpenoid found in natural resources like edible mushroom Inonotus obliquus. We established a rat model of diabetic-breast cancer by treating female Sprague-Dawley rats with streptazotocin (STZ) at 35 mg/kg followed by induction of breast cancer by administration of 7,12-dimethylbenz(a)anthracene (DMBA) at 10 mg/kg. Diabetes development in experimental rats was confirmed by measuring fasting blood glucose levels and oral glucose tolerance test (OGTT), and other biochemical assays were performed. Histological evaluation of pancreas was performed. The proliferation of breast tumor was measured by immunohistochemical staining for PCNA, cleaved-caspase-3 and TUNEL staining for apoptosis, and β-catenin. Results of the study demonstrate that inotodiol lowered the blood glucose levels in SD rats as well as reduced plasma levels of cholesterol, triglyceride, and high-density lipoprotein. The tumor proliferation marker PCNA was reduced by inotodiol. It downregulated the expression of β-catenin and its downstream targets (c-Myc and Cyclin D1) followed by apoptosis induction. Conclusively, results suggest that inotodiol regulates blood glucose levels in diabetic rats and then controls proliferation of breast tumor progression by inducing apoptosis via downregulation of β-catenin signaling. It further suggests that inotodiol can be a preventive approach in managing dietary chronic conditions like diabetic-breast cancer.

Topics: Animals; Apoptosis; beta Catenin; Blood Glucose; Body Weight; Cell Proliferation; Diabetes Mellitus, Experimental; Disease Models, Animal; Down-Regulation; Female; Gene Expression Regulation, Neoplastic; Glucose Tolerance Test; Hypoglycemic Agents; Lanosterol; Mammary Neoplasms, Animal; Pancreas; Rats, Sprague-Dawley; Signal Transduction; Streptozocin